The goal of this project is to define the interrelationships among microbial antigens, lymphocytes and macrophages in the immune repsonse to infectious diseases of man. Particular emphasis is on the correlation between functional activation of macrophages consequent to infection and their role as helper or suppressor cells modulating the immune response. The responses of circulating cells from normal individuals and patients with active tuberculosis to tuberculin and other bacterial products will be evaluated first. Standard separation techniques will be utilized to define the reponses of peripheral blood mononuclear cells and the component B and T lymphocytes and monocytes. In vitro assays of lymphocyte function will include antigen and mitogen-induced 3H-Thymidine incorporation and lymphokine production. Assays of macrophage activation will consist of quantitative attachment to plastic, killing of schistosomula of Schistosoma mansoni and tumors and production of arginase and prostaglandins. Suppressor cell function will be defined by depletion, add-Back and Cell-mixing techniques. Correlations will be sought among macrophage activation and helper or suppressor function as defined by these assays. These studies should allow dissection of some of the control mechanisms relevant in humor tuberculosis. They will evaluate the hypothesis that macrophage activation during infection may particulate in regulation of T lymphocyte activity by a negative feedback-type mechanism. These studies may prove important in understanding the expression of tuberculous disease. They also have the potential of suggesting alterations in the therapy of tuberculosis, and the use of BCG in immunoadjuvant therapy. The mechanisms of immunoregulation investigated here also could prove important in the large number of diseases in which suppressor adherent cell activity have been described including chronic fungal infections, Hodgkin's disease and other tumors, schistosomiasis, sarcoidosis and systemic lupus erythematosus.